Abstract Details

Title Investigating the Effect of Teriflunomide on Brain Volume Loss in the Phase 3 TOPIC Study

Topic Multiple Sclerosis

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-046

Objective To evaluate teriflunomide’s effect on brain volume loss independent of its effect on focal inflammatory disease activity in post-hoc analyses of the Phase 3 TOPIC (NCT00622700) study.

Background Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing forms of MS. The TOPIC study evaluated teriflunomide in patients with a first clinical episode suggestive of MS.

Design/Methods Patients were randomized to placebo, teriflunomide 7 mg or 14 mg for ≤108 weeks. Structural Image Evaluation using Normalisation of Atrophy (SIENA) assessed percent brain volume change (PBVC) at years 1 and 2. Independent effects of teriflunomide on PBVC were assessed using two regression analyses in patients with complete MRI data. An unadjusted model evaluated the effect of treatment (teriflunomide 14 mg vs placebo) on PBVC, then an adjusted model, adding active lesions (contrast-enhancing T1w lesions and/or new/enlarging T2w lesions) (yes/no) and relapses (yes/no), was compared to the unadjusted model. The relative difference between models represents the estimated treatment effect on PBVC independent of the effect on active lesions and relapses.

Results At year 2, in the unadjusted model, mean PBVC (95% CI) was −0.78% (−0.86, −0.70) in the placebo group (n=69) and −0.60% (−0.67, −0.52) in the 14 mg group (n=87); the estimated treatment effect was 0.18% (P<0.0001). In the adjusted model, mean PBVC was −0.79% (−0.88, −0.70) in the placebo group and −0.62% (−0.70, −0.54) in the 14 mg group; the estimated treatment effect was 0.17% (P<0.0001). The estimated treatment effect of teriflunomide 14 mg on PBVC independent of its effects on focal damage (relative difference between models) was 95.2%. Similar results were observed at year 1.

Conclusions Most of teriflunomide’s effect on PBVC appears to result from its effect on diffuse brain changes, independent of its effect on focal lesions and relapses.

Authors/Disclosures
Till Sprenger PRESENTER	No disclosure on file
	No disclosure on file
Patrick Vermersch (CHR de Lille)	Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AB Science. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Imcyse. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS-Celgene. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ad Scientiam. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for La revue des microbiotes. The institution of Patrick Vermersch has received research support from Roche. The institution of Patrick Vermersch has received research support from Sanofi.
	No disclosure on file
	No disclosure on file
Pamela A. McCombe, MD (Dr PA McCombe Medical Pty Ltd)	Dr. McCombe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. McCombe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. McCombe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme. The institution of Dr. McCombe has received research support from Motor Neurone Disease Resaerch Institute of Australia.
John A. Lincoln, MD, PhD (McGovern Medical School, UTHealth)	The institution of Dr. Lincoln has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. Dr. Lincoln has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Lincoln has received research support from Deaprtment of Defense. The institution of Dr. Lincoln has received research support from National Institutes of Health. The institution of Dr. Lincoln has received research support from EMD-Serono. Dr. Lincoln has received intellectual property interests from a discovery or technology relating to health care.
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	Dr. Kappos has nothing to disclose.
Niels Bergsland (Buffalo Neuroimaging Analysis Center / State University of New York At Buffalo)	Prof. Bergsland has nothing to disclose.
Michael G. Dwyer III, MD, PhD (Buffalo Neurological Analysis Center)	Dr. Dwyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Keystone Heart, Ltd. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Dwyer has received research support from Novartis. The institution of Dr. Dwyer has received research support from Keystone Heart, Ltd. The institution of Dr. Dwyer has received research support from Bristol Myers Squibb. The institution of Dr. Dwyer has received research support from Roche.
Steven J. Cavalier, MD, FAAN (SC Consulting)	No disclosure on file
Nora Roesch	No disclosure on file
Kathleen C. Somera-Molina, PhD	Dr. Somera-Molina has received personal compensation for serving as an employee of Biogen. Dr. Somera-Molina has received stock or an ownership interest from Biogen.
Elizabeth Poole	No disclosure on file
Robert Zivadinov, MD, PhD, FAAN (Buffalo Neuroimaging Analysis Center)	The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Omnicuris. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Myrobalan. Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen.

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